摘要:

AbstractPregnant rats were injected im with 0.5 mg/kg triamcinolone acetonide (TAC) on day 12, 13, or 14 of gestation and the fetuses were examined for cleft palate on day 20. All three TAC‐treated groups showed an increased proportion of fetuses with cleft palate compared to an untreated control group. Only the group treated on day 13 showed a significant increase in the proportion of litters affected. This indicates that day 13 of gestation is the most sensitive day for cleft palate induction by TAC in the rat.Pregnant rats were then treated on day 13 of gestation with either TAC, triamcinolone (TA), or cortisol. TAC was 59 times as potent as TA in inducing cleft palate, with ED50values of 1.1 mg/kg and 65 mg/kg respectively. Cortisol induced a significant increase in cleft palates at 500 mg/kg, but the efficacy of this compound was too low to calculate an ED50and relative teratogenic potency value. Other developmental abnormalities including umbilical hernias, resorption, and fetal death resulted from TAC treatment. Fetal growth retardation was produced by all three compounds. The rank order of teratogenic potency was determined to be TAC>TA>cortiso

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<313::AID-TCM1770030402>3.0.CO;2-6

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractCell suspensions from whole embryos were obtained on the 12th day of gestation from treated pregnant female mice. For the present experiments five model mutagens—BaP, bleomycin, mitomycin C, procarbazine, and TEM—were chosen for their different modes of action in inducing chromosomal aberrations. Time‐response and dose‐response were studied for chromosomal aberrations induced by transplacental treatment of mouse embryos. All five known mutagens gave a positive response in the present system. The maximum time of response varied from compound to compound and was found as early as 3h after treatment with the G2‐clastogen bleomycin or as late as 18h after treatment with the bifunctional alkylating agent TEM. Chromatid breaks and exchanges increased with dose in all instances. The correlations between clastogenic, carcinogenic, and teratogenic effects are discussed. It is concluded that the transplacental cytogenetic test may be applicable to identify chemicals that exhibit all three p

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<321::AID-TCM1770030403>3.0.CO;2-2

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractN‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) induces fetal asymmetric limb malformations with exposure of pregnant mice to 50 mg/kg on day 11 of gestation. Hindlimbs were more frequently malformed than forelimbs, and a fourfold greater incidence of postaxial ectrodactyly was found in left forelimbs than in right forelimbs, and a two fold excess in left hindlimbs compared to right hindlimbs. The level of cell death and mitotic index were measured in forelimbs and hindlimbs from treated and control embryos at 1, 4, 18, 24, 48, and 72 hr after exposure to ascertain if these parameters could be correlated with the differential teratogenic susceptibility of the limbs. An increase in necrotic index was first detected in treated limbs at 4 hr, increased at 18 hr, peaked at 24 hr, and began declining at 48 hr to reach the control baseline at 72 hr. At 24 hr, the correlation between the level of cell death and susceptibility of malformation was the strongest, with the left hindlimb having a necrotic index of 58%, the right hindlimb 47%, the left forelimb 30% and the right forelimb 12%. In both forelimbs and hindlimbs, MNNG treatment initially depressed mitotic activity followed by an elevation at 48 hr relative to controls. The magnitude of the depression, extent of the elevation, and overall pattern of mitotic activity could not be uniformly related to limb defects. These results indicate that the amount of cell death in limb buds at 24 hr after MNNG exposure may predict target organ susceptibility. Depressions in mitotic activity and alterations in the pattern of mitosis were also observed which were not as clearly correlated with the incidence of malformations as was the amount of

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<335::AID-TCM1770030404>3.0.CO;2-T

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractCytosol receptor binding of 17β‐estradiol was demonstrated in the uterus of the late‐gestation, fetal rhesus monkey. Sucrose density gradient analysis performed in low‐ionic strength buffer indicated a binding component with a sedimentation coefficient of 6–7 S. Under high‐ionic strength conditions, the component shifted to a sedimentation coefficient of approximately 4 S. The specificity of the receptor for estrogens was indicated by inhibition of [3H]estradiol binding by both natural and synthetic estrogen competitors, but not by progesterone. Saturation analysis indicated a high degree of nonspecific binding with saturation of specific binding occurring at 2–3 nM. Computer‐assisted Scatchard analysis of the data resolved a one‐receptor model having a limited number of binding sites and an apparent dissociation constant of 10−10M. The interaction of estrogens with the fetal uterus and the cellular mechanisms which permit this interaction are discussed in relation to the development of models for extrapol

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<355::AID-TCM1770030405>3.0.CO;2-K

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractPrimary cell‐mediated microbial mutagenesis assays have been shown to be useful in detecting specific target organ genotoxic activity. The lack of a standard protocol for these assays, however, makes interlaboratory comparisons difficult. In order to standardize the hepatocyte‐mediatedSalmonella typhimuriummutagenesis assay, incubation and activation conditions for the plate incorporation and preincubation assays were examined using two aromatic amines, 2‐aminofluorene (AF) and 2‐acetylaminofluorene (AAF). Direct comparison of two preincubation protocols demonstrated the necessity for the hepatocytes to be present during the two‐ to three‐day plate incubation period. An examination of various preincubation times showed relatively minor differences between 15 and 90 minutes. The preincubation and plate incorporation protocols were directly compared using both hamster and rat hepatocytes. For both preincubation and plate incorporation, the optimum concentration of hepatocytes was shown to be 1 × 106/plate. Direct evaluation of various hepatocyte‐mediated bacterial protocols should facilitate future interlaboratory comparisons using a more standard

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<367::AID-TCM1770030406>3.0.CO;2-C

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThis study was designed to investigate the possible genotoxic and teratogenic actions of diphenyl (DP), diphenyl ether (DPE), and their eutectic mixture, in a comparative approach including different test systems. Two microbial systems and a metazoan model were used: (1) diploid D7 strain ofSaccharomyces cerevisiae; (2)Salmonella typhimuriumstrains TA100, TA98, TA1535, TA1537, TA1538, TA1532, TA2636; and (3) sea urchins (Paracentrotus lividusandSphearechinus granularis).Both compounds resulted in severe toxicity in all of test organisms at levels ≥ 10−5M (∼ 2 ppm). DP caused genetic effects in yeast with and without activating system, while the two chemicals appeared to be ineffective inSalmonellaup to toxic levels. The action of DP and DPE on sea urchins resulted in developmental defects and mitotic abnormalities, following exposure of embryos or by pretreatment of sperm or eggs. In this system DPE appeared to be more effective than DP by about one order of magnitude (minimal active concentrations: 10−5M vs 10−4M).The eutectic mixture, industrially used as a heat transfer medium, was tested in its virgin and used form, for genotoxicity and embryotoxicity. The latter appeared to be more effective than the virgin eutectic. This increase in the embryoand genotoxicity of the used eutectic may be related to the appearance of newly formed compounds in the heat transfer process. These compounds have been separated by high‐pressure liquid chromatography and detected by

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<377::AID-TCM1770030407>3.0.CO;2-6

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:4<::AID-TCM1770030401>3.0.CO;2-0

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY